ER and Nutrient Stress Promote Assembly of Respiratory Chain Supercomplexes through the PERK-eIF2α Axis.
Activating Transcription Factor 4
/ genetics
Adenosine Triphosphate
/ metabolism
Animals
Apoptosis
Cell Line
Cell Survival
/ genetics
Electron Transport Complex I
/ genetics
Electron Transport Complex IV
/ genetics
Endoplasmic Reticulum
/ genetics
Endoplasmic Reticulum Stress
/ genetics
Energy Metabolism
/ genetics
Eukaryotic Initiation Factor-2
/ genetics
Glucose
/ metabolism
Humans
Mice
Mitochondria
/ genetics
Mitochondrial Diseases
/ genetics
Mutation, Missense
/ genetics
Nutrients
/ metabolism
Phosphorylation
Serine-Arginine Splicing Factors
/ genetics
Signal Transduction
eIF-2 Kinase
/ genetics
ATF4
ER stress
PERK
hexosamine pathway
mitochondria
mitochondrial cristae
mitochondrial diseases
nutrient stress
protein glycosylation
respiratory chain supercomplexes
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
06 06 2019
06 06 2019
Historique:
received:
19
12
2018
revised:
20
02
2019
accepted:
25
03
2019
pubmed:
27
4
2019
medline:
23
10
2019
entrez:
27
4
2019
Statut:
ppublish
Résumé
Endoplasmic reticulum (ER) stress and unfolded protein response are energetically challenging under nutrient stress conditions. However, the regulatory mechanisms that control the energetic demand under nutrient and ER stress are largely unknown. Here we show that ER stress and glucose deprivation stimulate mitochondrial bioenergetics and formation of respiratory supercomplexes (SCs) through protein kinase R-like ER kinase (PERK). Genetic ablation or pharmacological inhibition of PERK suppresses nutrient and ER stress-mediated increases in SC levels and reduces oxidative phosphorylation-dependent ATP production. Conversely, PERK activation augments respiratory SCs. The PERK-eIF2α-ATF4 axis increases supercomplex assembly factor 1 (SCAF1 or COX7A2L), promoting SCs and enhanced mitochondrial respiration. PERK activation is sufficient to rescue bioenergetic defects caused by complex I missense mutations derived from mitochondrial disease patients. These studies have identified an energetic communication between ER and mitochondria, with implications in cell survival and diseases associated with mitochondrial failures.
Identifiants
pubmed: 31023583
pii: S1097-2765(19)30235-7
doi: 10.1016/j.molcel.2019.03.031
pmc: PMC6555668
mid: NIHMS1527039
pii:
doi:
Substances chimiques
ATF4 protein, human
0
COX7A2L protein, human
0
Eukaryotic Initiation Factor-2
0
SCAF1 protein, human
0
Activating Transcription Factor 4
145891-90-3
Serine-Arginine Splicing Factors
170974-22-8
Adenosine Triphosphate
8L70Q75FXE
Electron Transport Complex IV
EC 1.9.3.1
EIF2AK3 protein, human
EC 2.7.11.1
eIF-2 Kinase
EC 2.7.11.1
Electron Transport Complex I
EC 7.1.1.2
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
877-890.e6Subventions
Organisme : NIDDK NIH HHS
ID : F32 DK105679
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA181217
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK089883
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121452
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
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